Different cytokine profile and eosinophil activation are involved in rhinovirus‐ and RS virus‐induced acute exacerbation of childhood wheezing

Abstract

Because little information is available on eosinophil activation and cytokine response in virus-induced wheezing, we attempted to detect respiratory viruses and measure eosinophil cationic protein (ECP), and 27 types of cytokines/chemokines in both serum and nasal secretions from children with wheezing. This study was an observational, case-control investigation of 267 subjects, who were visited and/or hospitalized with acute respiratory symptoms (with wheezing: men, 115; women, 59; mean/median age, 3.6/3.0 years) or who were visited for regular physical examination and treatment (non-symptomatic wheezing: men, 48; women, 31; mean/median, 5.0/4.7 years), and 14 control subjects (controls: men, 9; women, 5; mean/median, 3.6/3.7 years). We detected viruses in nasal secretions from 174 patients with acute exacerbations of wheezing using antigen detection kits or reverse transcription-polymerase chain reaction, followed by direct DNA sequencing analysis. We measured peripheral eosinophil counts, and serum concentrations of ECP and 27 cytokines/chemokines using a multiplex bead-based assay in patients with wheezing or non-symptomatic wheezing. We also examined nasal ECP and 27 cytokines/chemokines in patients with wheezing. Of 174 samples from wheezing exacerbations, rhinovirus was detected in 59; respiratory syncytial (RS) virus in 44; enterovirus in 17; other viruses in 19; and no viruses in 35. Serum concentrations of ECP, IL-5, IL-6, IL-1ra, and IP-10 were significantly elevated in rhinovirus-induced wheezing compared with non-symptomatic wheezing. Similarly, serum ECP, IL-5, and IP-10 were significantly higher in rhinovirus-induced wheezing than in controls. On the other hand, IL-1ra and IP-10, but not ECP and IL-5 were significantly higher in RS virus-induced wheezing than in controls. Furthermore, only IL-5 was significantly elevated in the rhinovirus group compared with the RS virus group in both serum and nasal secretions. Different cytokine profile and eosinophil activation might be involved in rhinovirus- and RS virus-induced acute exacerbation of childhood wheezing.

Differential Effects of Corticosteroids on Serum Eosinophil Cationic Protein and Cytokine Production in Rhinovirus- and Respiratory Syncytial Virus-Induced Acute Exacerbation of Childhood Asthma

“…The remaining secretions were frozen at –80°C until examination by further reverse transcription polymerase chain reaction (RT-PCR) and then by direct DNA sequencing analysis. The RT-PCR method used for rhinoviruses and RS virus was as previously described [15]. The DNA fragments were purified using a QIAquick PCR Purification kit (QIAGEN), and the nucleotide sequence was determined with an automated DNA sequencer ABI PRISM™ 310 Genetic Analyzer (Applied Biosystems, Foster City, Calif., USA) using a Big Dye Terminator v1.1 cycle sequencing kit (Applied Biosystems) [15].…”

“…The RT-PCR method used for rhinoviruses and RS virus was as previously described [15]. The DNA fragments were purified using a QIAquick PCR Purification kit (QIAGEN), and the nucleotide sequence was determined with an automated DNA sequencer ABI PRISM™ 310 Genetic Analyzer (Applied Biosystems, Foster City, Calif., USA) using a Big Dye Terminator v1.1 cycle sequencing kit (Applied Biosystems) [15]. For identification of the virus, newly determined sequences were compared with those available in the sequences using GenBank DNA databases (http://www.ncbi.nlm.nih.gov) and the standard nucleotide-nucleotide BLAST algorithm.…”

“…The ECP content in serum was measured with a fluoroenzyme immunoassay kit (Pharmacia, Uppsala, Sweden). Serum cytokines/chemokines were determined using a multi-cytokine detection system (Bio-Rad, Hercules, Calif., USA) following the manufacturer’s instructions, measured using a Luminex System (Austin, Tex., USA), and then quantified using Bio-Plex software (Bio-Rad) [15]. …”

Rhinoviruses

“…In those with an atopic background, eosinophilia was more common, and the virus isolation rate was higher than in the nonatopic group [ 394 ]. The cytokine and eosinophil activation profi les for HRSV-induced wheezing differ from those induced by HRV in which IL5 is signifi cantly higher in serum and nasal aspirates than for HRSV [ 118 ]. IP10 was the only cytokine signifi cantly elevated in all symptomatic wheezing groups [ 118 ].…”

“…The cytokine and eosinophil activation profi les for HRSV-induced wheezing differ from those induced by HRV in which IL5 is signifi cantly higher in serum and nasal aspirates than for HRSV [ 118 ]. IP10 was the only cytokine signifi cantly elevated in all symptomatic wheezing groups [ 118 ]. Signifi cantly higher rates of HRV detection with more obvious LRT symptoms are more common in children with asthma than in non-asthmatic populations [ 380 , 388 , 395 , 396 ].…”